Aspirin and the Anti-Phospholipid Syndrome

Graham Hughes is consultant rheumatologist at the Guy’s and St Thomas’ Hospital Trust, where he set up, in the Rayne Institute, the Lupus Arthritis Research Unit. He is Editor of the Journal Lupus. His main research interest is in systemic lupus erythematosus (SLE), not in itself a rare disease. However, he is seeing more and more people with anti-phospholipid syndrome, named internationally in 1992 as Hughes’ syndrome.
Women with it have recurrent spontaneous abortions, arterial and venous thromboses, and early myocardial infarctions. His interest in the disease started in 1975, in Jamaica, where he found women with ‘Jamaican neuropathy’, with meningomyelopathy, false positive syphilis tests, and thromboses in veins and arteries. In 1983 he wrote of recurrent thrombosis, abortion, cerebral disease, lupus and a circulating protein pro-coagulant co-factor, as the anti-phospholipid syndrome4.

Later in 1983, he added thrombocytopenia, livido reticularis, teenage migraine, demyelinating disease, Budd Chiari syndrome and dementia to the list of signs and symptoms. His colleague Nigel Harris developed the tests, and the offending pro-coagulant protein beta-2GP-1 is now well studied. Other protein co-factors that promote clotting include prothrombin. Dr Hughes’ group showed that people who possess anti-phospholipid antibodies and prothrombin antibodies have a 60% risk of thrombosis, and that many develop dementia.

Many patients with Hughes syndrome have memory loss and fail to report it, perhaps because they also have cognitive disorders. They improve neurologically when they start anticoagulants: indeed they know precisely, because they feel worse, when their INR has fallen. Among their neurological problems are choreo-athetosis and transverse myelopathy, and some are diagnosed as having multiple sclerosis. Most respond to warfarin.

Antiphospholipid antibodies bind to platelets, alter clotting factors and directly affect endothelial cell function. aspirin is the mainstay of treatment. The best data for its use are from pregnancy, in which Hughes syndrome is the most important thrombotic cause of recurrent pregnancy loss, which may occur as late as the seventh month. Simply explained, the placenta thromboses. Treatment with aspirin alone is remarkably successful. Among women with anti-phospholipid syndrome, whose previous pregnancies had a 19 per cent live birth rate, the current rate on aspirin is more than 70 per cent. Adding heparin may help further. There may be different subsets of the disease, depending on whether patients have arterial or venous thrombosis.

Perhaps the United States might not have existed had it not been for a case of Hughes’ syndrome. From 1683 onwards, Queen Anne had 18 miscarriages, a facial rash and arthritis. Her lack of an heir led to the invitation to the Hanoverians to take the throne, and it could be argued that their incompetence in managing their colonies led to the establishment of the USA.

Hughes syndrome causes many of the strokes that affect people under 45 years old. It is preventable, as are many cases of migraine, memory loss, deep vein thrombosis on the contraceptive pill, and some cases of Alzheimer’s disease. Any woman who has had one miscarriage, recurrent migraine, an early vascular event and is under 40 should be tested for it. Dr Hughes estimated that there are probably ten such women in each average-sized general practice.

Box 6. Anti-phospholipid syndrome is not uncommon, but do doctors recognise it? Young women with migraine, a facial rash, deep vein thrombosis on the pill and recurrent miscarriages should be tested for anti-phospholipid antibodies. The test is not expensive. aspirin, with perhaps added heparin, helps them greatly, may allow them to complete their pregnancies, and avoid mid-life onset of stroke or dementia.